Journal of Organic Chemistry 2002-06-28

A practical procedure for the large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate, a key intermediate for diltiazem.

Toshiyuki Furutani, Ritsuo Imashiro, Masanori Hatsuda, Masahiko Seki

Index: J. Org. Chem. 67(13) , 4599-601, (2002)

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Abstract

A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), was developed. Treatment of methyl (E)-4-methoxycinnamate 3 with chiral dioxirane, generated from chiral ketone 4, provided (-)-2 in 77% ee and 89% yield. The crude mixture of (-)-2 and 4 was efficiently separated by the use of novel and simple equipment performing a lipase-catalyzed transesterification and a continuous dissolution and crystallization to furnish the optically pure (-)-2 and recovery of 4 in 74% and 91% yield, respectively.